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Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes

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Abstract

Aims

Dioxin or dioxin-like compounds are ligands of the aryl hydrocarbon receptor (AhR), which is a ligand-activated nuclear transcription factor. There are limited studies about the association of serum AhR ligand activities and T2DM. Our objective was to investigate the association of serum AhR ligand activities with T2DM and its related metabolic parameters.

Methods

This case–control study involved 83 subjects with T2DM as well as age-, sex-, and body mass index (BMI)-matched subjects with impaired glucose tolerance (IGT, n = 130) and normal glucose tolerance (NGT, n = 83). Serum AhR ligand activities were measured using a cell-based AhR ligand assay and standardized as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDDeq, pmol/l).

Results

The T2DM group had the highest AhR ligand activities compared to the IGT and NGT groups [median (interquartile range), 68.1 (53.1, 81.5), 60.2 (45.8, 75.1), and 53.3 (46.1, 63.7) pmol/l, respectively; P = 0.003]. In the multivariate analysis, the log2-transformed TCDDeq levels were significantly associated with the risk of T2DM after adjusting for age, sex, and BMI (odds ratio 2.26, 95 % confidence interval 1.34–3.82; P = 0.002). In nondiabetic subjects, serum AhR ligand activities showed a positive correlation with fasting glucose and insulin concentrations and the homeostasis model assessment of insulin resistance, but showed a negative correlation with adiponectin concentrations.

Conclusions

Serum AhR ligand activities were higher in the T2DM group and were correlated with the parameters of insulin resistance. Further investigation is required to elucidate the causal relationship between AhR ligand activity and T2DM.

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Acknowledgments

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Education, Science and Technology; NRF-2006-2005410) and partly by the NRF grant funded by the Korea government (Ministry of Science, ICT, and Future Planning; NRF 2008-0061888).

Conflict of interest

Eun Roh, Soo Heon Kwak, Hye Seung Jung, Young Min Cho, Youngmi Kim Pak, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee declare that they have no conflict of interest to disclose.

Ethical standard

Ethics approval was obtained from the institutional review board of the Seoul National University Hospital in Seoul, Korea.

Human and animal rights disclosure

The study was approved by the Seoul National University Hospital Institutional Review Board and therefore performed in accordance with the ethical standards of the Helsinki Declaration of 1975, as revised in 2013.

Informed consent disclosure

All study subjects provided informed consent.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Hospital, Seoul, 110-744, Korea

    Eun Roh, Soo Heon Kwak, Hye Seung Jung, Young Min Cho, Kyong Soo Park & Seong Yeon Kim

  2. Department of Internal Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 110-744, Korea

    Eun Roh, Young Min Cho, Kyong Soo Park & Seong Yeon Kim

  3. Department of Physiology, Kyung Hee University College of Medicine, Seoul, 130-701, Korea

    Youngmi Kim Pak

  4. Department of Internal Medicine, Eulji University College of Medicine, Seoul, 139-711, Korea

    Hong Kyu Lee

  5. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, 110-744, Korea

    Eun Roh & Kyong Soo Park

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  1. Eun Roh
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Corresponding author

Correspondence to Kyong Soo Park.

Additional information

Managed by Massimo Federici.

Eun Roh and Soo Heon Kwak have contributed equally to this work.

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Roh, E., Kwak, S.H., Jung, H.S. et al. Serum aryl hydrocarbon receptor ligand activity is associated with insulin resistance and resulting type 2 diabetes. Acta Diabetol 52, 489–495 (2015). https://doi.org/10.1007/s00592-014-0674-z

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  • DOI: https://doi.org/10.1007/s00592-014-0674-z

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